Alzheimer's disease and atherosclerosis
are progressive degenerative syndromes that together afflict more
than 50% of the population in Western societies. Their prevalence
and socioeconomic impact is

steadily increasing along with average
life expectancy.

Our work has identified several fundamental
molecular mechanisms that are common to both of these superficially
unrelated diseases. They are mediated by a class of ancient and
evolutionarily highly conserved cell surface receptors known as
the LDL receptor gene family.

The core of this family consists of seven structurally closely
related multifunctional receptors that share partly overlapping
roles in such diverse biological processes as receptor-mediated
endocytosis, regulation of extracellular protease activity, hormone
transport, and intercellular signaling. The range of physiological
functions in which the receptors are involved includes lipid metabolism,
neuronal migration during brain development, neurotransmission,
axonal transport, vitamin metabolism, and the control of cellular
proliferation. All members of the family are also receptors for
Apolipoprotein E (ApoE), a major risk factor gene for late-onset
Alzheimer’s disease. One of our goals is to understand
how the interaction of ApoE and other physiological ligands with
its receptors affects the cell biology of the neuron.